Substantial efforts have been directed to developing tools useful for early diagnosis and treatment of the various forms of cancer. Nonetheless, a definitive diagnosis is often dependent on exploratory surgery which is inevitably performed after the disease has advanced past the point when early treatment may be effected. Further, many treatment methods are general and fail to specifically target cancer cells. One promising method for early diagnosis and treatment of various forms of cancer is the identification of specific biochemical moieties, termed antigens, present on the surface of cancerous cells. Antibodies which will specifically recognize and bind to the antigens present on the surfaces of cancer cells potentially provide powerful tools for the diagnosis and treatment of the particular malignancy. Tumor specific cell surface antigens have previously been identified for certain melanomas, lymphomas, malignancies of the colon and reproductive tract. Thus, cell surface markers and antibodies which specifically recognize such a cell surface marker are valuable in the early detection and treatment of cancers.
Tumor specific antigens may also be useful in tumor imaging techniques. Imaging techniques have become an important element of early detection for many cancers. But imaging is not simply used for detection. Imaging is also important for determining the stage (telling how advanced the cancer is) and the precise locations of cancer to aid in directing surgery and other cancer treatments, or to check if a cancer has returned.
Tumor specific antigens may also be useful in methods of radio-immunotherapy. The treatment of cancer by radio-immunotherapy involves injecting the patient with a radioactive isotope connected to a specific cancer cell vector such as a monoclonal antibody (i.e., a radioimmunoconjugate), with the aim of selectively destroying targeted tumor cells. During radioactive decay, photons, electrons or even heavier particles are emitted and damage or kill cells along their trajectory.
Human aspartyl (asparaginyl) β-hydroxylase (HAAH), also known as aspartate β-hydroxylase (ASPH) is normally localized to the endoplasmic reticulum, however upon cellular transformation it is translocated to the cell surface. Over-expression of the enzyme HAAH has been detected in many cancers tested including lung, liver, colon, pancreas, prostate, ovary, bile duct, and breast. HAAH is highly specific for cancer and is not significantly present in adjacent non-affected tissue, or in tissue samples from normal individuals. HAAH functions to hydroxylate aspartyl or asparaginyl residues within EGF-like domains of specific proteins. While the natural substrates of HAAH remain unknown, potential target proteins containing EGF-like domains include those involved in cellular signaling (e.g., notch) and/or cell/extra-cellular matrix interactions (e.g., tenascin).